The main objective of this program is to evaluate the relationship between changes in membrane structure and function and aging. In our first program project grant interesting and important alterations in membrane functions as the animal ages were noted. We wish to pursue, extend and introduce new approaches to our study of membrane alteration and aging. The projects are divided into two general categories: those on the cardiovascular system and those on the central nervous system (CNS). There will also be studies performed on the kidney and salivary gland. Projects on the cardiovascular system involve: 1) characterization of electrophysiological, ionic and mechanical responses of cardiac muscle under stress (hypoxia) and its response to drugs as a function of age; 2) characterization of hemodynamics, autonomic nervous system activity and the membranes of the vasculature. Hemodynamic considerations are included to determine whether such changes may explain or contribute to changes in cardiac, CNS and vasculature membrane alterations; 3) ionic fluxes change during aging and Na plus K ions activated ATPase may be involved in these changes. Characterization of the activity of this enzyme will be conducted not only in the heart but brain and kidney. Kidney pathology suggests possible alterations in Na plus K ions ATPase activity. Projects on the CNS will involve principally the adenyl cyclase system. Sensitivity studies of the adenyl cyclase-cyclic AMP will be performed to determine whether under denervation or reduced neural input compensation for this is achieved in young and older animals to different degrees. Salivary and heart adenyl cyclase will be studied also. We anticipate by studying similar enzymes in different systems and inducing in the preparation 'stress' that further insight into the nature and role of membrane changes as the animal ages will be achieved.